Hippocampal BDNF expression in a tau transgenic mouse model.
ABSTRACT Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid deposits and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau proteins. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor playing a critical role in hippocampal synaptic plasticity and memory and whose levels have been shown reduced in AD brains. While recent data support a pivotal role of β-amyloid peptides towards BDNF decrease, whether Tau pathology impacts on BDNF expression remains unknown so far. In the present study, we have evaluated this relationship using quantitative PCR, Western blot and ELISA in the THY-Tau22 transgenic strain, known to display a progressive development of both hippocampal AD-like Tau pathology and memory impairments. We observed that Tau pathology was not associated with down-regulation of BDNF at the protein and mRNA levels in this model, suggesting that the alteration of BDNF homeostasis observed in AD patients' brains might rather be ascribed to amyloid pathology.
- SourceAvailable from: Jillian Belrose[show abstract] [hide abstract]
ABSTRACT: Alterations in the expression and signaling of brain-derived neurotrophic factor (BDNF) and the precursor to nerve growth factor (NGF), proNGF, play a role in the neuronal and cognitive dysfunction of Alzheimer's disease. Aggregated amyloid-β has been shown to down-regulate specific BDNF transcripts in Alzheimer's disease, but the role of tau pathology in neurotrophin dysregulation has not been investigated. We measured levels of BDNF mRNA and protein using real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay and proNGF protein using Western blotting in parietal cortex of subjects with tauopathies, neurodegenerative diseases exhibiting tau pathology without amyloid-β accumulation. We observed a significant increase in the level of proNGF protein in Pick's disease and a significant decrease in BDNF mRNA and protein levels in Pick's disease and corticobasal degeneration, but no neurotrophin alterations in progressive supranuclear palsy. The decrease in total BDNF mRNA levels in these tauopathies was predominantly due to down-regulation of transcript IV. These findings implicate tau pathology in neurotrophin dysregulation, which may represent a mechanism through which tau confers toxicity in Alzheimer's disease and related non-Alzheimer's dementias.Neurobiology of aging 10/2013; · 5.94 Impact Factor